The use of surgical prosthetic devices, otherwise known as implants, is well known in various surgical applications, such as reconstructive surgery, for example, in the replacement of hip joints or the like. Use of surgical prosthetic devices such as plates, nails, pins, screws, and specially formed parts are commonly implanted into the skeletal structure of animals for the replacement of missing structural parts, or as permanent anchoring devices for maintaining a fixed relationship between the portions of a fractured bone. Rapid integration of these devices with the patient's natural bone, referred to as osseointegration, is desired, so that the strength of the interface is rapidly and maximally achieved. This reduces healing time, recovery time, and failure rate of the implant. These principles also apply to dental implants.
The application of cell adhesion domains (such as the RGD motif) to tissue engineering has become a subject of intense interest. The RGD (argininyl-glycinyl-aspartyl or Agr-Gly-Asp) tripeptide sequence (found in extracellular matrix clycoproteins such as type I collagen, bone sialoprotein [BSP], osteopontin, osteonectin, vitronectin, fibronectin, etc.) binds to cell surface integrins such as .alpha..sub.5.beta..sub.3 (reviewed by Butler, Connect. Tissue Res., 23:123-136, 1989 and Butler, J. Biol. Buccale, 19:83-89, 1991). Certain of these proteins may participate by acting as a seed or regulator of mineral crystal growth and/or by directing cells and their associated functions to specific sites within the tissue. The presence of the tripeptide sequence RGD, the distribution of these proteins, and their association with mineral suggest that these phosphoproteins may have a multifunctional role during mineralized tissue formation whereby they may, firstly, initiate and regulate mineralization, and secondly, direct dynamics by mediating cell attachment to the matrix (McKee et al., Anat. Rec., 234:479-492, 1992 and McKee et al., J. Bone Miner. Res., 8:485-496, 1992).
It is towards the identification of peptides capable of promoting bone mineralization and osseointegration of bone implants that the present invention is directed.
The citation of any reference herein should not be construed as an admission that such reference is available as "Prior Art" to the instant application.